Cephalosporin compounds containing the chemical substructure of formula (I) are important antibacterial therapeutic agents. The manufacture of these cephalosporin compounds is typically performed in a series of synthetic chemical reactions. Reducing the number of synthetic chemical reactions and associated purification steps can increase product yield and decrease the time for production, thereby increasing efficiency and decreasing production costs.

Syntheses of antibiotic cephalosporin compounds containing the substructure of formula (I) typically require two reactions for the formation of a 7-carboxamide moiety: (1) deprotection (i.e., removal of a protecting group) of the 7-amino group, and (2) acylation of the 7-amino group to form the 7-carboxamide moiety. One example of this two-step procedure is disclosed in U.S. Pat. No. 5,134,138 (see FIG. 2). Most cephalosporin antibiotics can be manufactured in an analogous way. Ceftolozane (CXA-101, FR264205) is a cephalosporin antibiotic compound, a synthesis of which is disclosed in U.S. Pat. No. 7,129,232. Additional cephalosporin antibiotic compounds include the compounds of Table 2. There remains an unmet need to identify novel manufacturing processes for synthesizing cephalosporin compounds comprising the chemical substructure of formula (I), including methods for formation of a 7-carboxamide moiety from a protected 7-amino group with fewer chemical synthetic steps.